This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The research is designed to determine the prevalence and risk factors of pulmonary hypertension in children and adolescents with sickle cell disease, and to determine the role of hypoxic response in its pathogenesis. In this regard, proliferative vascular responses mediated by hypoxia inducible factor-regulated pathways and nitric oxide scavenging will be compared between patients with SCD and patients with Chuvash polycythemia, another hematological disorder characterized by increased risk for PHT. High throughput microarray and genotyping technologies will be employed to identify candidate gene polymorphisms involved in pathologic responses to hypoxia in SCD and CP patients with and without PHT.